The Down Syndrome Core has been established to assess clinical and neuropathological changes in DS patients similar to those in AD. The brains of DS individuals over 40 years of age invariably have senile plaques and neurofibrillary tangles, the hall mark of AD neuropathology. Similarly, most plaques occur in the amygdala, hippocampus, temporal and parietal cortices, with somatosensory pathways less affected. Unlike the general population. DS individuals show an earlier age of onset for dementia that runs a more rapid and severe course. The prevalence of AD neuropathology in the non-DS mentally retarded population is similar to the general population, suggesting that the increased rate of AD in DS is not simply a function of mental retardation. Thus, DS provides an opportunity in a compressed time course to examine disease-related parameters at a clinical and basic science level, and provide insight into the AD pathogenesis. The primary function of the DS Core has been to provide subjects and tissues for ADRC investigators to examine behavioral and histopathological correlates of DS and AD. Interaction with other cores has been a corner stone for the DS core, promoting interacting among investigators and extending the scope of clinical, experimental and neuropathologic studies. Since initiation of the DS Core over 50 DS patients have been enrolled in longitudinal studies. Ages of participants range from 12 to 59 years (57% males, and 43% females). To provide DS tissues, a repository has been established in conjunction with the UCI AD Neuropathology subcore. Various neuroanatomical studies indicate substantial homologies in plaque development in DS and AD brain. MR imaging studies of the aging DS brain has also shown similarities with AD. Interactions with the Imaging core for 3D MRI, MR spectroscopy and PET studies promises to provide new insights into anatomical and functional aspects of both AD and DS. Observations from AD research are also being applied to DS to characterize behavioral deficits that may occur. Deterioration of olfactory function is an early marker of AD. For example, in a longitudinal study, DS patients are being assessed with a standardized tests of olfaction. Cognitive, emotional, and behavioral functions have been assessed in DS and AD patients, and longitudinal data will continue to be collected. The focus of these studies is to direct and differentiate early cognitive, emotional, and behavioral correlates in demented DS adults. As the DS core develops it has become apparent that clinical interventions are needed. Behavioral and pharmacological interventions applied to AD are proposed for the DS group. DS subjects with and without dementia will be assessed and trained using a computer-based program designed to measure skill level in areas of attention, discrimination, visual short-term memory, and visual sequencing. The emphasis of these studies will be on identifying early markers of cognitive decline, and to assess change in patients who participate in a selegiline and alpha-tocopherol clinical trial. The drug trial will parallel the AD clinical trial. Thus, the DS core offers a comprehensive program for clinical and neuropathological characterization of individuals with DS. supports a variety of projects related to aging and dementia and provides subjects and tissues for other investigators. Interactions with other ADRC cores compliment DS core activities to promote a more detailed understanding of AD pathogenesis and contribute to the development of effective therapeutic interventions.